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Abstract Background Patients with irresectable stage III or metastatic melanoma presenting with poor prognostic factors are usually treated with a combination of immune checkpoint inhibitors (ICIs), consisting of ipilimumab and nivolumab. This combination therapy is associated with severe immune related adverse events (irAEs) in about 60% of patients. In current clinical practice, patients are usually treated with ICIs for up to two years or until disease progression or the occurrence of unacceptable AEs. The incidence of irAEs gradually increases with duration of treatment. While durable tumour responses have been observed after early discontinuation of treatment, no consensus has been reached on optimal treatment duration. The objective of the Safe Stop IPI-NIVO trial is to evaluate whether early discontinuation of ICIs is safe in patients with irresectable stage III or metastatic melanoma who are treated with combination therapy. Methods The Safe Stop IPI-NIVO trial is a nationwide, multicentre, prospective, single-arm, interventional study in the Netherlands. A total of 80 patients with irresectable stage III or metastatic melanoma who are treated with combination therapy of ipilimumab-nivolumab and have a complete or partial response (CR/PR) according to RECIST v1.1 will be included to early discontinue maintenance therapy with anti-PD-1. The primary endpoint is the rate of ongoing response at 12 months after start of ICI. Secondary endpoints include ongoing response at 24 months, disease control at different time points, melanoma specific and overall survival, the incidence of irAEs and health-related quality of life. Discussion From a medical, healthcare and economic perspective, overtreatment should be prevented and shorter treatment duration of ICIs is preferred. If early discontinuation of ICIs is safe for patients who are treated with the combination of ipilimumab-nivolumab, the treatment duration of nivolumab could be shortened in patients with a favourable tumour response. Trial registration ClinicalTrials.gov ID NCT05652673, registration date: 08–12-2022.

Abstract Background Interest in applying a complex systems approach to understanding socioeconomic inequalities in health is growing, but an overview of existing research on this topic is lacking. In this systematic scoping review, we summarize the current state of the literature, identify shared drivers of multiple health and health behavior outcomes, and highlight areas ripe for future research. Methods SCOPUS, Web of Science, and PubMed databases were searched in April 2023 for peer-reviewed, English-language studies in high-income OECD countries containing a conceptual systems model or simulation model of socioeconomic inequalities in health or health behavior in the adult general population. Two independent reviewers screened abstracts and full texts. Data on study aim, type of model, all model elements, and all relationships were extracted. Model elements were categorized based on the Commission on Social Determinants of Health framework, and relationships between grouped elements were visualized in a summary conceptual systems map. Results A total of 42 publications were included; 18 only contained a simulation model, 20 only contained a conceptual model, and 4 contained both types of models. General health outcomes (e.g., health status, well-being) were modeled more often than specific outcomes like obesity. Dietary behavior and physical activity were by far the most commonly modeled health behaviors. Intermediary determinants of health (e.g., material circumstances, social cohesion) were included in nearly all models, whereas structural determinants (e.g., policies, societal values) were included in about a third of models. Using the summary conceptual systems map, we identified 15 shared drivers of socioeconomic inequalities in multiple health and health behavior outcomes. Conclusions The interconnectedness of socioeconomic position, multiple health and health behavior outcomes, and determinants of socioeconomic inequalities in health is clear from this review. Factors central to the complex system as it is currently understood in the literature (e.g., financial strain) may be both efficient and effective policy levers, and factors less well represented in the literature (e.g., sleep, structural determinants) may warrant more research. Our systematic, comprehensive synthesis of the literature may serve as a basis for, among other things, a complex systems framework for socioeconomic inequalities in health.

There is increased recognition that determinants of health should be investigated in a life-course perspective. Retirement is a major transition in the life course and offers opportunities for changes in physical activity that may improve health in the aging population. The authors examined the effect of retirement on changes in physical activity in the GLOBE Study, a prospective cohort study known by the Dutch acronym for “Health and Living Conditions of the Population of Eindhoven and surroundings,” 1991–2004. They followed respondents (n = 971) by postal questionnaire who were employed and aged 40–65 years in 1991 for 13 years, after which they were still employed (n = 287) or had retired (n = 684). Physical activity included 1) work-related transportation, 2) sports participation, and 3) nonsports leisure-time physical activity. Multinomial logistic regression analyses indicated that retirement was associated with a significantly higher odds for a decline in physical activity from work-related transportation (odds ratio (OR) = 3.03, 95% confidence interval (CI): 1.97, 4.65), adjusted for sex, age, marital status, chronic diseases, and education, compared with remaining employed. Retirement was not associated with an increase in sports participation (OR = 1.12, 95% CI: 0.71, 1.75) or nonsports leisure-time physical activity (OR = 0.80, 95% CI: 0.54, 1.19). In conclusion, retirement introduces a reduction in physical activity from work-related transportation that is not compensated for by an increase in sports participation or an increase in nonsports leisure-time physical activity. [ABSTRACT FROM AUTHOR]

The roles and responsibilities of radiation therapists (RTTs) are many and varied. Professional expectations are influenced by the technology available, as well as the level of autonomy RTTs have in their daily practice. This professional range requires RTTs to possess a unique set of ever evolving skills, posing challenges from an educational perspective. Teaching these "advanced skills" has been the ambition the ESTRO Advanced Skills in Modern Radiotherapy course. In the 10th year of this course, the Faculty look back and reflect on how our programme has evolved and what it has achieved., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

In the Netherlands, child abuse affects about 100.000 children resulting in at least 17 child fatalities a year. General practitioners' (GPs) health care position is of vital importance for recognising and managing child abuse. In this Clinical Lesson, using three illustrating cases, we discuss how GPs' suspicion of child abuse may arise including the role of gut feelings, and what the mandatory national guideline on child abuse means for the follow-up. We also clarify the role of the Dutch Child Abuse Counselling and Reporting Centre (CACRC) in the process. A first lesson is that any doubts about child abuse should lead to action because diagnostic failure has serious consequences for vulnerable children. A second lesson is that asking CACRC for anonymous advice how to deal with a situation may certainly have added value. Finally, we advise CACRC to invest in building a relationship of trust with the collaborating partners.

Learning rules by which cell shape impacts cell function would enable control of cell physiology and fate in medical applications, particularly, on the interface of cells and material of the implants. We defined the phenotypic response of human bone marrow-derived mesenchymal stem cells (hMSCs) to 2176 randomly generated surface topographies by probing basic functions such as migration, proliferation, protein synthesis, apoptosis, and differentiation using quantitative image analysis. Clustering the surfaces into 28 archetypical cell shapes, we found a very strict correlation between cell shape and physiological response and selected seven cell shapes to describe the molecular mechanism leading to phenotypic diversity. Transcriptomics analysis revealed a tight link between cell shape, molecular signatures, and phenotype. For instance, proliferation is strongly reduced in cells with limited spreading, resulting in down-regulation of genes involved in the G2/M cycle and subsequent quiescence, whereas cells with large filopodia are related to activation of early response genes and inhibition of the osteogenic process. In this paper we were aiming to identify a universal set of genes that regulate the material-induced phenotypical response of human mesenchymal stem cells. This will allow designing implants that can actively regulate cellular, molecular signalling through cell shape. Here we are proposing an approach to tackle this question.

Background: Despite the fact that vaccines save 2-3 million lives worldwide every year, a percentage of children are not getting appropriately vaccinated, thus leading to disease outbreaks. One of the major reasons of low vaccine uptake in Europe is vaccine hesitancy, contributing to the recent measles outbreaks. Monitoring of vaccine hesitancy is valuable in early identification of vaccine concerns., Methods: We performed an eighteen country European survey on parents' attitudes and behaviors regarding their children's immunization. Parents having at least one child 1-4 years old were mostly recruited by primary care paediatricians to reply to a web-based questionnaire. The questionnaire was developed by the European Academy of Paediatrics Research in Ambulatory Setting Network steering committee, based on similar surveys. An individual level hesitancy score was constructed using the answers to 21 questions, and correlations of the score with socio-demographic characteristics and types of providers were explored. To assess inter country differences, a country level self -reported confidence was defined., Results: Fifty six percent and 24% of 5736 respondents defined themselves as "not at all hesitant", and "somewhat hesitant", respectively. Parents who consulted general practitioners were more hesitant than parents who consulted pediatricians (p < 0.05). Consultation with homeopathists was associated with the highest reported hesitancy (p < 0.05). Vaccine confidence was highest in Portugal and Cyprus, and lowest in Bulgaria and Poland., Conclusion: The majority of parents in Europe believe in the importance of childhood vaccination. However, significant lack of confidence was found in certain European countries, highlighting the need for continuous monitoring, awareness and response plans. The possible influence of different types of healthcare providers on parental decisions demonstrated for the first time in our survey, calls for further research. Monitoring and continuous medical education efforts aimed mostly at those professionals who might not be likely to recommend vaccination are suggested., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: Combined paediatric and forensic medical expertise to interpret physical findings is not available in Dutch healthcare facilities. The Dutch Expertise Centre for Child Abuse (DECCA) was founded in the conviction that this combination is essential in assessing potential physical child abuse. DECCA is a collaboration between the three paediatric hospitals and the Netherlands Forensic Institute. DECCA works with Bayes' theorem and uses likelihood ratios in their conclusions., Design: We present the implementation process of DECCA and cross-sectional data of the first 4 years., Participants: Between 14 December 2014 and 31 December 2018, a total of 761 advisory requests were referred, all of which were included in this study. An advisee evaluation over the year 2015 was performed using a self-constructed survey to gain insight in the first experiences with DECCA., Results: 761 cases were included, 381 (50.1%) boys and 361 (47.4%) girls (19 cases (2.5%) sex undisclosed). Median age was 1.5 years (range 1 day to 20 years). Paediatricians (53.1%) and child safeguarding doctors (21.9%) most frequently contacted DECCA. The two most common reasons for referral were presence of injury/skin lesions (n=592) and clinical history inconsistent with findings (n=145). The most common injuries were bruises (264) and non-skull fractures (166). Outcome of DECCA evaluation was almost certainly no or improbable child abuse in 35.7%; child abuse likely or almost certain in 24.3%, and unclear in 12%. The advisee evaluations (response rate 50%) showed that 93% experienced added value and that 100% were (very) satisfied with the advice., Conclusion: Data show growing interest in the expertise of DECCA through the years. DECCA seems to be a valuable addition to Dutch child protection, since advisee value the service and outcome of DECCA evaluations. In almost half of the cases, DECCA concluded that child abuse could not be substantiated., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

Objective: Exercise-induced bronchoconstriction (EIB) is a specific morbidity of childhood asthma and a sign of insufficient disease control. EIB is diagnosed and monitored based on lung function changes after a standardized exercise challenge test (ECT). In daily practice however, EIB is often evaluated with self-reported respiratory symptoms and spirometry. We aimed to study the capacity of pediatricians to predict EIB based on information routinely available during an outpatient clinic visit. Methods: A clinical assessment was performed in 20 asthmatic children (mean age 11.6 years) from the outpatient clinic of the MST hospital from May 2015 to July 2015. During this assessment, video images were made. EIB was measured with a standardized ECT performed in cold, dry air. Twenty pediatricians (mean years of experience 14.4 years) each evaluated five children, providing 100 evaluations, and predicted EIB severity based on their medical history, physical examination, and video images. EIB severity was predicted again after additionally providing baseline spirometry results. Results: Nine children showed no EIB, four showed mild EIB, two showed moderate, and five showed severe EIB. Based on clinical information and spirometry results, pediatricians detected EIB with a sensitivity of 84% (95% CI 72-91%) and a specificity of 24% (95% CI 14-39%).The agreement between predicted EIB severity classifications and the validated classifications after the ECT was slight [Kappa = 0.05 (95% CI 0.00-0.17)]. This agreement still remained slight when baseline spirometry results were provided [Kappa = 0.19 (95% CI 0.06-0.32)]. Conclusion: Pediatricians' prediction of EIB occurrence was sensitive, but poorly specific. The prediction of EIB severity was poor. Pediatricians should be aware of this in order to prevent misjudgement of EIB severity and disease control.

Background: The StartingTogether program (in Dutch SamenStarten) is a family-centred method for early identification of social-emotional and behavioural problems in young children. Nurses in preventive child health care find it challenging to: determine family issues and need for care; provide education; refer to social services; increase parent empowerment. To mitigate these challenges, we developed and evaluated the StartingTogether App, offering nurses and parents conversational support, tailored education and information on social services., Methods: A mixed method design, consisting of a qualitative evaluation of the StartingTogether App, with group discussions with nurses ( N  = 14) and a pilot test ( N  = 5), and a randomized controlled trial, evaluating the effectiveness of the app. Nurses ( N  = 33) made home visits to parents ( N  = 194), in teams with or without the app. Nurses were surveyed on the challenges experienced during visits. Parents ( N  = 166) were surveyed on their satisfaction with health care and app. Nurses were interviewed on the benefits and barriers to use the app., Results: Parents with the StartingTogether App were more satisfied with the visits than parents without ( p  = .002). Parents with a high educational level were more satisfied with the visits than the parents with a low educational level. With the app, their satisfaction level was similar ( p  < .001). Nurses using the app felt more equipped to communicate with parents ( p  = .012) and experienced that parents were more knowledgeable and skilled ( p  = .001). Parents felt that with the app the nurse was more polite ( p  = .02), listened more carefully ( p  = .03), and had more time ( p  = .02). Nurses with the app gave parents more opportunity to ask questions ( p  = .001) and gave clearer answers ( p  < .001). The qualitative evaluation indicated that some nurses needed extra time to develop the habit of using the app., Conclusions: The StartingTogether App contributes to parents' satisfaction with home visits. An interaction effect between parents' educational level and rating of home visits indicated that the app has an additional value for parents with a lower educational level. Applying mobile applications, such as the StartingTogether App, potentially has a positive effect on communication between nurses and parents about the family situation in relation to parent empowerment and the child's development., Trial Registration: The study is registered with ISRCTN under the number ISRCTN12491485, on August 23, 2018. Retrospectively registered., Competing Interests: The study protocol was approved by the ethics committee of TNO (Netherlands Organisation for Applied Scientific Research) and registered with ISRCTN under the number ISRCTN12491485, on August 23, 2018. Retrospectively registered. Parents, nurses and their team leaders gave their informed written consent for participating in the study. The audit complied with the privacy law and administration of patient data.Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Objectives: A novel triage approach to routine assessments was introduced to improve the efficiency of Preventive Child Healthcare (PCH): PCH assistants carried out pre-assessments of all children and sent the children with suspected health problems to follow-up assessments conducted by a physician or nurse. This two-step approach differed from the usual approach, in which physicians or nurses assessed all children. This study was aimed to examine the impact of triage and task shifting on care for children at risk identified by PCH or parents and schools., Design and Participants: An observational prospective cohort design was used, with an analysis of the basic registration data from the preventive health assessments for 1897 children aged 5 to 6, and 10 to 11, years from a sample of 41 schools stratified by socioeconomic status, region of PCH service and urbanisation., Setting: A comparison was made between two PCH services in the Netherlands that used the triage approach and two PCH services that provided the usual approach., Main Outcome Measures: The primary outcome measures were the referral rates to either additional PCH assessments or external services. The secondary outcome measures were the rates of PCH assessments requested by, for example, parents and schools., Results: Overall, a higher referral rate to additional PCH assessments was found for the triage approach than for the usual approach (OR 1.3, 95% CI 1.0 to 1.6), mainly in the age group of 5 to 6 years (OR 1.9, 95% CI 1.3 to 2.7). We found a lower rate of referral to external services in the triage approach (OR 0.4, 95% CI 0.3 to 0.7) and a higher referral rate to PCH assessments on request (OR=4.6, 95% CI 3.0 to 7.0)., Conclusions: The triage approach provides extra opportunities to deliver PCH assessments and PCH assessments on request for children at risk. Further research is needed into the cost benefits of the triage approach., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Intravenous immunoglobulins (IVIGs) are the cornerstone in the treatment of pregnancies at risk for fetal and neonatal alloimmune thrombocytopenia (FNAIT). The most commonly used dose is 1.0 g/kg/week, not based on any dose-finding study. IVIG is an expensive multidonor human blood product with dose-related side effects. Our aim was to describe the amount of severe thrombocytopenia according to two different doses of IVIG., Study Design and Methods: We performed a cohort study, where two dosage regimes of IVIG were evaluated in the treatment of pregnant women suffering from FNAIT with a previous affected child without intracranial hemorrhage (ICH). Cases, treated with 0.5 or 1.0 g/kg/week, were selected from the international multicenter No IntraCranial Hemorrhage (NOICH) registry. Outcome was neonatal platelet (PLT) count at birth and amount of severe thrombocytopenia. Furthermore the appearance of ICH was analyzed., Results: A total of 109 women were included in the study, 46 in the 0.5 IVIG group and 63 in the 1.0 IVIG group. There was no difference in PLT count at birth (mean, 112 vs. 119; crude difference, 7; confidence interval [CI], -37.4 to 23.7]) and incidence of severe thrombocytopenia (<30 × 10(9) /L; n = 7/46 vs. n = 7/63; odds ratio, 1.43 [CI, 0.46-4.42]). No ICH occurred., Conclusion: In pregnancies with FNAIT with a previous affected child without ICH, treatment with IVIG in a weekly dose of 0.5 or 1.0 g/kg results in comparable neonatal PLT count at birth and degree of thrombocytopenia., (© 2016 AABB.)

Purpose: Current solutions for navigated spine surgery remain hampered by restrictions in surgical workflow as well as a limited versatility and applicability. Against this background, we report the first experience of navigated spinal instrumentation with the mobile AIRO(®) intraoperative computed tomography (iCT) scanner., Methods: AIRO(®) iCT was used for navigated posterior spinal instrumentation of 170 screws in 23 consecutive patients operated on in our Department between the first use of the system in May 2014 and August 2014. The indications for AIRO(®) were based on the surgical region, anatomical complexity and the need for >3 segment instrumentation. Following navigated screw insertion, screw positions were confirmed intraoperatively by a second iCT scan. CT data on screw placement accuracy were retrospectively reviewed and analyzed by an independent observer., Results: AIRO(®)-based spinal navigation was easy to implement and successfully accomplished in all patients, adding around 18-34 min to the net surgery time. A systematic description of the authors' approach, setup in the OR and workflow integration of the AIRO(®) is presented. Analysis of screw placement accuracy revealed 9 (5.3%) screws with minor pedicle breaches (<2 mm). A total of 7 screws (4.1%) were misplaced >2 mm, resulting in an accuracy rate of 95.9%., Conclusions: The AIRO(®) system is an easy-to-use and versatile iCT for navigated spinal instrumentation and provides high pedicle screw accuracy rates. Although the authors' experience suggests that the learning curve associated with AIRO(®)-based spinal navigation is steep, a systematic user-based approach to the technology is required.

Background: We investigated the detection of health problems in preventive child health care (PCH) by a novel triage approach for routine health assessments. In the triage approach, all children were preassessed by a physician's assistant, and only those in need of follow-up were assessed by a PCH physician or nurse. In the traditional approach, all children were assessed by a PCH physician or nurse., Methods: A prospective cohort design was used with data on routine assessments of 1897 children aged 5 to 6 and 10 to 11 years. Primary outcomes were the detection of overweight, visual disorders, and psychosocial problems, with type of approach (traditional vs triage) as independent variable. To assess the severity of health problems, BMI, Snellen, Strengths and Difficulties Questionnaire, and Child Behavior Checklist, scores were compared for both approaches in subgroups of children with overweight, visual disorders, or psychosocial problems., Results: No significant differences were found between the approaches in terms of the detection of incident cases of overweight, visual disorders, and psychosocial problems. Significantly higher Strengths and Difficulties Questionnaire scores were found in the subgroup with psychosocial problems when the triage approach was used. Marginal differences between the approaches were found for severity of overweight in the subgroup of overweight children., Conclusions: A novel triage approach to PCH resulting in less involvement of physicians and nurses in routine assessments appears to detect health problems as effectively as the traditional approach in place. More research is needed to determine the long-term outcomes of the 2 approaches., (Copyright © 2016 by the American Academy of Pediatrics.)

Purpose: The aim of this study was to quantify interfractional esophageal tumor position variation using markers and investigate the use of markers for setup verification., Materials and Methods: Sixty-five markers placed in the tumor volumes of 24 esophageal cancer patients were identified in computed tomography (CT) and follow-up cone-beam CT. For each patient we calculated pairwise distances between markers over time to evaluate geometric tumor volume variation. We then quantified marker displacements relative to bony anatomy and estimated the variation of systematic (Σ) and random errors (σ). During bony anatomy-based setup verification, we visually inspected whether the markers were inside the planning target volume (PTV) and attempted marker-based registration., Results: Minor time trends with substantial fluctuations in pairwise distances implied tissue deformation. Overall, Σ(σ) in the left-right/cranial-caudal/anterior-posterior direction was 2.9(2.4)/4.1(2.4)/2.2(1.8) mm; for the proximal stomach, it was 5.4(4.3)/4.9(3.2)/1.9(2.4) mm. After bony anatomy-based setup correction, all markers were inside the PTV. However, due to large tissue deformation, marker-based registration was not feasible., Conclusions: Generally, the interfractional position variation of esophageal tumors is more pronounced in the cranial-caudal direction and in the proximal stomach. Currently, marker-based setup verification is not feasible for clinical routine use, but markers can facilitate the setup verification by inspecting whether the PTV covers the tumor volume adequately., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Our purpose was to quantify changes in local dynamic stability (LDS) of the lumbar spine, hip, knee, and ankle in response to changes in lower limb segment mass, as well as to quantify temporal adaptations to segment loading during treadmill walking. Results demonstrate that increased mass distal to a joint yields either the maintenance of, or increased stabilization of, that particular joint relative to the unloaded condition. Increased mass proximal to a particular joint resulted in joint destabilization. The hip and ankle LDS were observed to change temporally, independent of segment loading condition, suggesting adaptation to walking on a treadmill interface.

Objectives: To study the impact of lifestyle factors on dental caries experiences in addition to the effect of demographic characteristics at the ages of 9, 15, and 21 years., Methods: The data were obtained from the study 'Oral health in children and adolescents in the Netherlands'. Data were collected through questionnaires and a clinical oral examination. Because the DMFS count data were highly skewed with a peak at zero, the negative binomial hurdle model was used for the analyses. The first part of the hurdle predicted the probability of having caries experience or not, and the second part predicted the degree of caries experience., Results: For the 9- and 15-year-old age groups, the breakfast frequency per week was related with having caries experience, while the frequency of brushing teeth per day was related with the degree of caries experience. In addition, the number of food and drinks consumed per day was important for the younger age group. These relations were not found in the 21-year-olds age group., Conclusions: Findings of this study suggest that components to promote structure and regularity, including having breakfast and the number of food and drink moments, may be important to include in programs to prevent dental caries in children., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background and Purpose: Neoadjuvant chemoradiation (nCRT) followed by surgery is considered curative intent treatment for patients with resectable esophageal cancer. The aim was to establish hemodynamic aspects of changes in heart volume and to explore whether changes in heart volume resulted in clinically relevant changes in the dose distribution of radiotherapy., Methods: A prospective study was conducted in patients who were treated with nCRT consisting of carboplatin and paclitaxel concomitant with radiotherapy (41.4 Gy/1.8 Gy per fraction). Physical parameters, cardiac volume on CT and Cone beam CT, cardiac blood markers and cardiac ultrasound were obtained., Results: In 23 patients a significant decrease of 55.3 ml in heart volume was detected (95% CI 36.7-73.8 ml, p<0.001). There was a decrease in both systolic (mean decrease 18 mmHg, 95% CI 11-26 mmHg, p<0.001) and diastolic blood pressure (mean decrease 8 mmHg, 95% CI 2-14 mmHg, p=0.008) and an increase in heart rate with 6 beats/min (95% CI 1-11 beats/min, p=0.021). Except for Troponin T, no change in other cardiac markers and echocardiography parameters were observed. The change in heart volume did not result in a clinically relevant change in radiation dose distribution., Conclusion: Heart volume was significantly reduced, but was not accompanied by overt cardiac dysfunction. All observed changes in hemodynamic parameters are consistent with volume depletion. Adaptation of the treatment plan during the course of radiotherapy is not advocated., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

In children who are born prematurely or whose birth weight is too low for gestational age (small for gestational age (SGA)) intensive care and follow up are desirable.However, obstacles include the shared care of children born very preterm (< 32 weeks of gestation) by paediatricians, general practitioners, youth health care service (and other professionals) and the identification of possible late onset health problems in children born late preterm (32-37 weeks of gestation). This guideline is multidisciplinary and evidence based and is relevant to all professionals involved in the care of this group of children. The main recommendations are: (a) timely and complete transfer of information after discharge from hospital; (b) structured exchange of information in aftercare; (c) assigning a case manager to each child; (d) monitoring growth and development by adjusting age for preterm birth, and (e) using special growth charts for children born preterm to evaluate growth and development.

A more prominent role for the youth healthcare physician: Youth Healthcare physicians reflect on the Dutch Paediatric Association (NVK) guideline entitled 'Gastro-oesophageal reflux (disease) in children aged 0-18 years'. This guideline states that medicinal treatment is given to these children too often. Dutch Youth Healthcare physicians see a large number of children with gastro-oesophageal reflux, with or without additional symptoms. The most common symptoms (crying and diminished weight gain) might be present even in the absence of reflux. Parents should be given advice and support when they are worried about reflux, crying or low weight gain. A lower weight gain curve on the growth chart is normal in breastfed children, and crying might be due to factors such as lack of routine or stimulus reduction. Overfeeding might also be the cause. Parents should be supported and followed up, with or without treatment, as necessary. Youth Healthcare professionals could perform this task.

Case Description: We present two patients with frequent school absences. Patient A is a 12-year-old boy, diagnosed with developmental coordination disorder. When his mother visits the youth community health doctor, he shows signs of an anxiety disorder with stress-related physical symptoms. Patient B is a 15-year-old boy whose teacher suspects a gaming and internet addiction. After consulting the youth community health doctor, he is referred to a psychologist for further diagnosis of a social anxiety disorder., Conclusion: Frequent school absenteeism is associated with psychological problems. After excluding physical causes referral for further psychiatric assessment is recommended. As the medical advisor of the school, the youth community health doctor can play a role in this process.

Background: Dutch Youth health care is an easily accessible service where parents can ask for support for the healthy development of their children. The majority of the screenings and medical examinations show no abnormalities. Sometimes there is doubt about the severity of symptoms: the line between healthy variation and diseases or abnormalities can be rather fine., Case Description: Patient A, a 3-month-old baby, showed signals of hypotonia and growth deficit while breastfeeding. Additional nutrition restored his growth and muscle tone. Patient B, a 4-week-old baby, displayed severe hypotonia. This appeared to be based on Werdnig-Hoffman disease. He died at the age of 4 months., Conclusion: Distinguishing conditions in the normal range from rare and severe conditions is daily work for every physician and is based on knowledge and experience. Combining symptoms and signs is essential. The youth health care physician sees mostly healthy children and is aware of the great variation within that group. This makes the youth health care physician an expert in distinguishing conditions in the normal range from rare and severe conditions.

The Dutch Youth Act (2015) has to resolve serious problems among young people, prevent inappropriate medicalisation, and realise efficiency. Participation and empowerment are terms often used. At the moment Dutch youth healthcare doctors monitor children on a regular basis and assess situations based on the national Public Health Status and Forecast Report (PHSF; VTV in Dutch) 'health field' context model. We discuss two children with behavioural problems at school and at home. Based on a detailed analysis and after excluding medical issues, in the first case the youth health care doctor advised participation in a sporting activity for those of limited financial means, and in the second case, the child was not referred for psychiatric consultation as simple adjustments at school were sufficient. The VTV 'health field' context model which Dutch youth health care doctors apply, links medical knowledge with the detection of non-medical issues. This expertise, combined with the knowledge of potential local intervention measures, can result in improved participation at home and at school. It is important that the family physician and other medical specialists recognise this expertise.

We investigated the change in cardiac volume over the course of chemoradiotherapy in 26 patients treated for esophageal cancer, using cone beam CT imaging. The cardiac volume reduced significantly, with a median reduction of 8%. A significant relationship with planned cardiac dose was not found., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: Undescended testis (UDT) or cryptorchidism is the most common genital anomaly seen in boys and can be treated surgically by orchidopexy. The age at which orchidopexy should be performed is controversial for both congenital and acquired UDT., Methods: A decision analysis is performed in which all available knowledge is combined to assess the outcomes of orchidopexy at different ages., Results: Without surgery, unilateral congenital UDT and bilateral congenital UDT are associated with average losses in quality-adjusted life-years (QALYs) of 1.53 QALYs (3% discounting 0.66 QALYs) and 5.23 QALYs (1.91 QALYs), respectively. Surgery reduces this QALY loss to on average 0.84 QALYs (0.21 QALYs) for unilateral UDT and 1.66 QALYs (0.40 QALYs) for bilateral UDT. Surgery at detection will lead to the lowest QALY loss of 0.91 (0.34) and 1.73 (0.60) QALYs, respectively, for unilateral and bilateral acquired UDT compared with surgery during puberty and no surgery. No sensitivity analysis is able to change the preferences for these strategies., Conclusions: Based on our decision analytic model using societal valuations of health outcomes, surgery for unilateral UDT (both congenital and acquired) yielded the lowest loss in QALYs. Given the modest differences in outcomes, there is room for patient (or parent) preference with respect to the performance and timing of surgery in case of unilateral UDT. For bilateral UDT (both congenital and acquired), orchidopexy at any age provides considerable benefit, in particular through improved fertility. As there is no strong effect of timing, the age at which orchidopexy is performed should be discussed with the parents and the patient. More clinical evidence on issues related to timing may in the future modify these results and hence this advice.

Background: Access to unpublished clinical study reports (CSRs) is currently being discussed as a means to allow unbiased evaluation of clinical research. The Institute for Quality and Efficiency in Health Care (IQWiG) routinely requests CSRs from manufacturers for its drug assessments. Our objective was to determine the information gain from CSRs compared to publicly available sources (journal publications and registry reports) for patient-relevant outcomes included in IQWiG health technology assessments (HTAs) of drugs., Methods and Findings: We used a sample of 101 trials with full CSRs received for 16 HTAs of drugs completed by IQWiG between 15 January 2006 and 14 February 2011, and analyzed the CSRs and the publicly available sources of these trials. For each document type we assessed the completeness of information on all patient-relevant outcomes included in the HTAs (benefit outcomes, e.g., mortality, symptoms, and health-related quality of life; harm outcomes, e.g., adverse events). We dichotomized the outcomes as "completely reported" or "incompletely reported." For each document type, we calculated the proportion of outcomes with complete information per outcome category and overall. We analyzed 101 trials with CSRs; 86 had at least one publicly available source, 65 at least one journal publication, and 50 a registry report. The trials included 1,080 patient-relevant outcomes. The CSRs provided complete information on a considerably higher proportion of outcomes (86%) than the combined publicly available sources (39%). With the exception of health-related quality of life (57%), CSRs provided complete information on 78% to 100% of the various benefit outcomes (combined publicly available sources: 20% to 53%). CSRs also provided considerably more information on harms. The differences in completeness of information for patient-relevant outcomes between CSRs and journal publications or registry reports (or a combination of both) were statistically significant for all types of outcomes. The main limitation of our study is that our sample is not representative because only CSRs provided voluntarily by pharmaceutical companies upon request could be assessed. In addition, the sample covered only a limited number of therapeutic areas and was restricted to randomized controlled trials investigating drugs., Conclusions: In contrast to CSRs, publicly available sources provide insufficient information on patient-relevant outcomes of clinical trials. CSRs should therefore be made publicly available. Please see later in the article for the Editors' Summary.

Continence problems can occur during childhood. This guideline is for the Dutch Youth Health Care (JGZ) and gives recommendations for the prevention, early detection and treatment of these problems. As a preventative measure advices for potty training should be started in children aged 18-24 months. If incontinence is present, it is important to take a history and carry out physical examination. In children over the age of 5 who are incontinent of urine the following are recommended: taking child out of bed, calendar with reward system, bedwetting alarm or voiding diary; children over the age of 8 can follow dry bed training. Faecal incontinence is often associated with constipation. Incontinent children with constipation are given advice about normal eating and exercise patterns. If this is not successful then laxatives are prescribed. The JGZ should refer further if there are indications of an underlying condition; if children over the age of 5 are wet during the day; if children are incontinent of faeces at night; if children are incontinent of faeces but not constipated; if children persistently wet the bed; if there is faecal incontinence despite counselling, and if medication needs to be prescribed.

There is a high incidence of skin disorders; these are also frequently encountered within Youth Healthcare (YHC). Some skin disorders are caused by an underlying disease, syndrome or child abuse. Therefore, detection of these causes in an early stage is important. Skin disorders can have a huge psychosocial impact on both child and parents. This is one of the reasons why prevention, detection, diagnosis, treatment, referral, and uniform advice and guidance are of great importance. The YHC Guideline examines counselling and advice, criteria for referral to primary or secondary healthcare, and skincare in general. It also describes the disorders that should be actively detected. The Guideline also looks at specific aspects of dark skins and ethnic diversity, and the impact of skin disorders on general wellbeing. The accompanying web-based tool includes argumentation and opinions from experts on more than 75 skin disorders, including illustrations and decision trees, to aid the drawing up of a treatment plan.

The objective of the evidence-based guidelines 'Asthma in children (ages 0-19)' for youth healthcare (CHC) is the prevention and reduction of asthma symptoms. The guidelines contain a lot of recommendations that apply to all disciplines in healthcare that deal with children. Primary prevention (preventing asthma): the main proven effective intervention is no smoking, neither passive nor active. Breastfeeding has a small protective effect. Starting at the first home visit at two weeks, the CHC nurse advises no smoking and to breastfeed. Secondary prevention (early detection): at all routine check-ups, the professional at CHC should inquire about signs of dyspnoea and wheezing. Patients suspected of having asthma should be referred to the GP. Tertiary prevention (reducing symptoms in children with asthma): the main advice is no smoking (neither passive nor active) and to follow the advice of the treating physician.

The objective of this study was to investigate the prevalence of methicillin-resistant Staphylococcus pseudintermedius (MRSP) in people, pets and the environment in households with a pet with a clinical MRSP-infection within the past year. Personnel and the environment at veterinary clinics were also screened. Nasal swabs (humans), nasal and perineal swabs (pets) and environmental wipes were examined using selective culturing. Twenty households were enrolled; 10/20 index cases still had clinical signs of infection at the start of the study and all were MRSP-positive. Of the remaining 10 index cases five were MRSP-positive in nasal and/or perineal samples. Five of 14 (36%) contact dogs and four of 13 (31%) contact cats were found MRSP-positive. In the households with an index case with clinical signs of infection 6/7 (86%) contact animals were MRSP-positive. MRSP was cultured from 2/45 (4%) human nasal samples. Domestic contamination was widespread as positive samples were found in 70% of the households and 44% of all environmental samples were MRSP-positive. In all but one of these MRSP-positive households the index case was still MRSP positive. Among the personnel in veterinary clinics 4/141 (3%) were MRSP-positive. MRSP was cultured from 31/200 environmental samples in 7/13 clinics at the first sampling and in 3/6 clinics the environment remained MRSP-positive after cleaning and disinfection indicating that current cleaning procedures often were unable to eliminate MRSP. These results show that transmission of MRSP between infected or colonized dogs and cats and healthy people does occur but is relatively uncommon, while transmission to contact pets occurs frequently, especially when the index case still has clinical signs of MRSP-infection., (Copyright © 2011 Elsevier B.V. All rights reserved.)

The main goal of this guideline for preventive child health care (PCHC) is to improve early detection of disorders that induce short stature. Based on research, evidence-based referral criteria for children aged 0-10 years with a short stature were formulated. These criteria are important for all professionals working with children, such as PCHC, general practitioners and paediatricians. Previous referral criteria dated 1997 and titled 'Diagnostics of short stature in children' had a very low specificity and were therefore considerably revised. They should no longer be applied. The guideline also provides information on the cause of short stature, psychosocial aspects and the use of growth hormone.

Objective: To assess the short- and long-term effects of 3 simple behavioral interventions to overcome nocturnal enuresis in young children., Study Design: We performed a randomized controlled trial in children aged four to five years with mono-symptomatic nocturnal enuresis (n = 570). The children were placed in one of four groups: (1) lifting to urinate and ask for a password; (2) the same as group 1, without a password; (3) using a reward system; or (4) a control group. Each participant was asked to carry out the appointed intervention for 6 months or until 14 consecutive dry nights occurred, which was the continence criterion. A follow-up was performed approximately 3 years after the study., Results: After 6 months, lifting the child to the toilet without the use of a password was the only intervention that resulted in significantly more dry children (37%) than the control group (21%). Three years later, both lifting groups had the highest (78%) and the control group the lowest (69%) percentage of dry children., Conclusions: The intervention lifting to urinate without the use of a password leads to more dry children compared with no active treatment in children aged 4 to 5 years with nocturnal enuresis.